Eisai initiates Phase III trial ofLenvima (lenvatinib) with everolimusor pembrolizumab to treat advanced renal cell carcinoma.

Eisai Co., Ltd.has announced the initiation of a global Phase III Clinical Study (Study 307, CLEAR Study) of its in-house developed multiple receptor tyrosine kinase inhibitor lenvatinib mesylate (lenvatinib) in respective combination regimens with the anticancer agent everolimus and the anti-PD-1 antibody pembrolizumab as a potential first-line treatment for advanced renal cell carcinoma. The CLEAR (Comparison of the efficacy and safety of Lenvatinib in combination with everolimus or pembrolizumab versus sunitinib alone in first-line treatment of subjects with advanced renal cell carcinoma) study is a multicenter, randomized, open-label Phase III clinical study to compare the efficacy and safety of lenvatinib/everolimus and lenvatinib/pembrolizumab versus sunitinib alone in first-line treatment in patients with advanced renal cell carcinoma. The primary outcome measure will be progression-free survival.

Comment:In May 2016, lenvatinib was approved in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy by the FDA in the United States. Furthermore, lenvatinib was approved in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor targeted therapy in Europe in August 2016.

The approvals were based on a Phase II clinical study (Study 205) that compared the safety and efficacy of Lenvima alone, and in combination with everolimus, in patients with unresectable advanced or metastatic renal cell carcinoma following one prior vascular endothelial growth factor-targeted therapy. From the results of the study, the group who received the combination of Lenvima plus everolimus demonstrated a significant extension in PFS,showing a median progression-free survival nearly three times that of everolimus alone (median PFS 14.6 months versus 5.5 months, respectively).The combination regimen resulted in a 63% reduction in the risk of disease progression or death compared with everolimus alone, while the objective response rate was 37% versus 6%, respectively.